Ral guanine nucleotide exchange factor with PH domain and SH3-binding motif 2 (RALGPS2)

Ral guanine nucleotide exchange factor with PH domain and SH3-binding motif 2 (RALGPS2) is a member of the guanine nucleotide exchange factor (GEF) family specifically activating the small GTPase RalA, but does not exhibit a Ras-binding domain[1][2][3]. RALGPS2 contains a Cdc25-like GEF domain, a central PxxP motif (allowing interactions with SH3 domains, such as those of Grb2 and phospholipase C gamma), and a C-terminal pleckstrin homology (PH) domain that binds phosphatidylinositol 4,5-bisphosphate and mediates membrane localization[1][2][3][4]. RALGPS2 is involved in cytoskeletal organization, causes morphological changes, and is essential for formation of tunneling nanotubes, which play roles in cell–cell communication relevant to cancer progression[4]. In cancer cell lines, RALGPS2 is necessary for cell survival and cell cycle progression, working partly independently of the canonical RalA/RalB GTPases, and influencing key cell cycle regulators such as Skp2, p27, and p21[6]. It is expressed in various tissues including testis, brain, and cancer cells[1][4]. RALGPS2 is considered a signaling protein with oncogenic relevance but is not currently associated with specific approved drugs or therapeutic targeting strategies[3][6].

Other names

RALGPS2KIAA0351FLJ10244FLJ25604dJ595C2.1Ras-specific guanine nucleotide-releasing factor RalGPS2RalA exchange factor RalGPS2Ral GEF with PH domain and SH3-binding motif 2